Identification of a cytokine-induced antiapoptotic molecule anamorsin essential for definitive hematopoiesis.
Identification of a cytokine-induced antiapoptotic molecule anamorsin essential for definitive hematopoiesis.
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DOI：
10.1084/jem.20031858
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发表时间：
2004-02-16
期刊：
影响因子：
--
通讯作者：
Kanakura Y
中科院分区：
文献类型：
--
作者：
Shibayama H;Takai E;Matsumura I;Kouno M;Morii E;Kitamura Y;Takeda J;Kanakura Y
许多生长因子和细胞因子可防止细胞凋亡。通过表达克隆方法，我们鉴定了一种新型抗凋亡分子Anamorsin，它与已知的凋亡调节分子如Bcl-2家族、caspase家族或信号转导分子没有任何同源性。在因子依赖性造血细胞系中，Anamorsin的表达完全依赖于生长因子（例如白细胞介素3、干细胞因子和血小板生成素）的刺激，并且Anamorsin的强制表达赋予了对体外生长因子剥夺引起的细胞凋亡的抵抗力。此外，Anamorsin被发现在体内充当抗细胞凋亡分子，因为Anamorsin−/−小鼠在妊娠晚期由于胎儿肝脏（FL）中的确定造血功能缺陷而死亡。尽管这些小鼠的 FL 中造血干细胞/祖细胞的数量没有减少，但骨髓细胞，特别是响应细胞因子的红细胞集落形成受到严重破坏。此外，Anamorsin−/− 红系细胞在终末成熟期间引发细胞凋亡。至于Anamorsin介导的细胞存活机制，微阵列分析显示，Anamorsin−/−小鼠的FL中Bcl-xL和Jak2的表达严重受损。因此，阿那莫辛被认为是造血必需的分子，介导各种细胞因子的抗凋亡作用。
Many growth factors and cytokines prevent apoptosis. Using an expression cloning method, we identified a novel antiapoptotic molecule named Anamorsin, which does not show any homology to known apoptosis regulatory molecules such as Bcl-2 family, caspase family, or signal transduction molecules. The expression of Anamorsin was completely dependent on stimulation with growth factors such as interleukin 3, stem cell factor, and thrombopoietin in factor-dependent hematopoietic cell lines, and forced expression of Anamorsin conferred resistance to apoptosis caused by growth factor deprivation in vitro. Furthermore, Anamorsin was found to act as an antiapoptotic molecule in vivo because Anamorsin−/− mice die in late gestation due to defective definitive hematopoiesis in the fetal liver (FL). Although the number of hematopoietic stem/progenitor cells in the FL did not decrease in these mice, myeloid, and particularly erythroid colony formation in response to cytokines, was severely disrupted. Also, Anamorsin−/− erythroid cells initiated apoptosis during terminal maturation. As for the mechanism of Anamorsin-mediated cell survival, a microarray analysis revealed that the expression of Bcl-xL and Jak2 was severely impaired in the FL of Anamorsin−/− mice. Thus, Anamorsin is considered to be a necessary molecule for hematopoiesis that mediates antiapoptotic effects of various cytokines.
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